The Philly mouse derived from the Swiss-Webster strain develops a cataract about 6 weeks after birth. The results of early studies have shown that in the lenses of these animals, the epithelial cells fail to undergo complete differentiation. Biochemically, a 27 kD protein apparently missing from the Philly lens was shown to be the betaB2-crystallin, which in the normal lens is a heat-stable protein. Investigation of the Philly mouse revealed that mRNA with approximately the same size as the normal betaB2 mRNA is present in the Philly lens. It was further shown that a protein present in the Philly lens is immunologically related to the betaB2 protein in the normal lens. This protein shares the same amino terminal as the normal betaB2 but lacks part of the carboxyl half of the protein. The altered protein is slightly smaller and has a more acidic isoelectric point than the normal lens betaB2-crystallin. cDNAs were cloned and sequenced for normal and Philly mouse betaB2-crystallin. The normal mouse betaB2 cDNA is 725 (bp) in length and has 618 bp of open reading frame. Deduced amino acid sequences suggest that the normal mouse betaB2 lacks a phosphorylation site at the C-terminal that is found in other mammals. The Philly mouse has a deletion of 12 nucleotides in the area encoding its fourth motif. The properties of the protein encoded with this deletion appear to be consistent with the earlier protein findings and may be responsible for the cataract formation.